Which Aspirin Dose and Preparation Is Best for the Long-Term Prevention of Cardiovascular Disease and Cancer? Evidence From a Systematic Review and Network Meta-Analysis

The evidence base on aspirin in primary prevention suggests that it can reduce significantly the risk of cardiovascular disease (CVD) events and cancer, especially colorectal, albeit increasing bleeding. There is, however, uncertainty on the optimal aspirin dose and preparation for primary prevention. We thus aimed to review main sources of evidence informing on daily dosage and preparation of aspirin for primary prevention of CVD and cancer. We collected and elaborated aspirin effectiveness and safety data from U.S. Preventive Services Task Force reports on aspirin in primary prevention, distinguishing average daily dose in < 100 mg, 100 mg, and > 100 mg. The following preparations were also systematically compared: enteric coated, controlled release, non-coated, or otherwise unspecified. Fixed-effect pairwise and network meta-analytic models were run in a frequentist framework. Eleven randomized trials were shortlisted, enrolling 104,101 subjects, followed for a median of 60 months. At pairwise analysis, aspirin was associated with significant reductions in death and CVD events, non-significant reductions in cancer death or incidence, and significant increases in the risk of intracranial and gastrointestinal (GI) bleeding. An average daily dose of 100 mg had the highest probability of reducing death, cancer death, and cancer incidence, whereas higher doses seemed superior for reducing CVD events, and 100 mg or less daily proved better tolerated. Coated preparations appeared more beneficial for death, cancer death, cancer incidence, and GI bleeding, whereas controlled release preparations appeared better for CVD events and non-coated ones for intracranial bleeding. In conclusion, an average daily dose of 100 mg of coated aspirin seems more likely to confer favorable preventive effects on death and cancer, with higher doses more appealing for CVD prevention and lower doses better tolerated.